Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “circulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,693 records · Page 94Linked to original sources
PubMed2003

Contribution of endothelin and its receptors to the regulation of vascular tone during exercise is different in the systemic, coronary and pulmonary circulation.

OBJECTIVES: Exercise-induced vasodilation is thought to be mediated through various vasodilator substances, but blunting the influence of vasoconstrictors such as ET may also play a role. However, the role of ET and its receptors in the regulation of systemic, pulmonary and coronary vascular resistance is incompletely understood. The aim of this study was to identify the contribution of ET-1 through the ET(A) and ET(B) receptors to the regulation of tone in the systemic, coronary and pulmonary beds at rest and during exercise. METHODS: Ten chronically instrumented swine were studied while running on a treadmill before and after ET(A) blockade (EMD122946) or ET(AB) blockade (tezosentan). RESULTS: At rest, EMD122946 resulted in vasodilation in the coronary and systemic circulation, evidenced by a decrease in coronary and systemic vascular resistance and an increase in coronary and mixed venous O(2)-saturation. These effects waned during exercise. The effect of tezosentan on the systemic vasculature was similar to that of EMD122946, whereas it was smaller in the coronary circulation. EMD122946 had no effect on the pulmonary vasculature, whereas tezosentan decreased pulmonary resistance but only during exercise. CONCLUSIONS: ET exerts a constrictor influence on the coronary and systemic circulation through the ET(A)-receptor, which decreases during exercise thereby contributing to metabolic vasodilation. ET exerts a tonic vasodilator influence on coronary resistance vessels through the ET(B)-receptor. Finally, ET exerts an ET(B)-mediated constrictor influence in the pulmonary vasculature during exercise.

Animals↗
PubMed1993

Cerebral blood flow and the hyperdynamic circulation of rats after portacaval anastomosis.

Both increased and decreased values of cerebral blood flow have been reported in liver disease. Furthermore, the relation between the cerebral circulation and the generalized hemodynamic disturbance seen in chronic liver disease with portal-systemic shunting has not been fully characterized. We studied this problem in a well defined model of the hyperdynamic circulation, the rat after portacaval anastomosis (PCA). Using the radioactive microsphere technique, cardiac output and regional blood flows were measured; regional vascular resistances were then calculated. While the fraction of cardiac output perfusing the splanchnic bed was significantly increased, the corresponding brain fraction was reduced. Blood flow to the cerebral hemispheres and midbrain was significantly decreased. Arterial vasodilatation was demonstrated by the fall in arterial pressure, systemic vascular resistance as well as splanchnic and renal resistances; cerebrovascular resistance, however, was unchanged. No relation between values of arterial pressure and cerebral blood flow was seen, making a failure of cerebrovascular autoregulation unlikely. The decrease in hemispheric and midbrain perfusion without changes in vascular resistance suggests that a drop in blood flow is appropriately coupled to a reduction in brain metabolism. The cerebral circulation does not participate in the hyperdynamic state that is seen in this model.

Animals↗
PubMedDate not supplied

Uncoupling the systemic circulation and the Ex Vivo circuit during experimental isolated liver perfusion.

Performing an ex vivo liver perfusion as a transient liver support requires perfusing the liver with a flow of 1 ml/min per kg of liver, which could reach 25% of the cardiac output when a human liver is used. This high flow could be detrimental in patients with acute liver failure. Therefore, in an ischemic-induced liver failure pig model, we developed a circuit allowing low flows going out of and into the systemic circulation, whereas the flow going through the ex vivo liver is maintained at a high value. This was obtained by uncoupling the ex vivo circuit from the systemic circulation. Ex vivo liver perfusion was performed in a closed circuit with a flow averaging 1 ml/min per kg of ex vivo liver (700 to 800 ml/min, according to the weight of the livers we used). It was linked to the systemic circulation with input and output flows equal to that used during hemodialysis (200 ml/min). Compared with previously reported direct circuits, this perfusion system was well tolerated from a circulatory point of view. After the induction of ischemic liver failure, the ex vivo liver perfusion led to an increase in urea, branched amino acids to aromatic amino acid ratio, and fractional clearance of indocyanine green and galactose and to a decrease in ammonia and lactic acid. This system allowed the ex vivo liver to keep its clearing properties despite a low extracorporeal flow. It represents an extracorporeal circuit that could be used in place of the direct extracorporeal high-flow liver perfusion.

Animals↗
PubMed1993

Effect of subcutaneous sumatriptan, a selective 5HT1 agonist, on the systemic, pulmonary, and coronary circulation.

BACKGROUND: Sumatriptan (GR43175) is a selective 5-hydroxytryptamine (5HT1) receptor agonist effective in the acute treatment of migraine. Recent in vitro experiments suggest that it has vasoactive properties in vascular beds distinct from the cerebral circulation. The object of this study was to assess the vasoactive effects of the standard 6-mg subcutaneous dose of sumatriptan used in migraine on the systemic and pulmonary circulations and the coronary artery vasculature. METHODS AND RESULTS: Ten patients undergoing diagnostic coronary arteriography were studied with digital subtraction angiography and invasive hemodynamic monitoring. After subcutaneous injection of sumatriptan, there was no significant change in heart rate or ECG morphology. There was a significant rise in the systemic (20%, p < 0.05 by ANOVA) and pulmonary artery (40%, p < 0.05 by ANOVA) pressures. There was no change in cardiac output, but there was a significant increase in total systemic (27%, p < 0.05) and total pulmonary vascular resistance (40%, p < 0.05). Sumatriptan caused a significant reduction (p < 0.001 by ANOVA) in mean absolute coronary artery diameter, from 4.36 +/- 1.60 mm at baseline to 3.67 +/- 1.49 mm (16%) at 10 minutes and to 3.63 +/- 1.49 mm (17%) at 30 minutes after injection. There were no clinical sequelae. CONCLUSIONS: Sumatriptan, a 5HT1 receptor agonist administered by the subcutaneous route, causes a vasopressor response in the systemic and pulmonary arterial circulations and coronary artery vasoconstriction.

Adult↗
PubMed1991

[A case of aortitis syndrome with coronary steal syndrome due to collateral circulation from the right coronary artery to intracranial vessels].

A 44-year old female with aortitis syndrome complained of precordial pain on effort. Exercise electrocardiograms revealed significant ST segment depression in leads II, III, aVF and V. Coronary arteriograms demonstrated no stenosis. However, the right coronary arteriogram revealed collateral circulation arising from the sinus node artery to the bilateral vertebral arteries and the left internal carotid artery. Collateral vessels in aortitis.syndrome arising from the coronary artery to the lung have been reported sporadically. However, to our knowledge, the collateral circulation from the coronary artery to intracranial vessels as seen in the present case has never been reported. In the present case, the left ventricular hypertrophy was observed on electrocardiograms and echocardiograms. It can not be denied that it was a cause of the angina pectoris. However, exercise myocardial scintigraphy showed transient myocardial ischemia at stress on the inferoposterior wall corresponding to leads II, III, aVF and V on electrocardiograms. Therefore, coronary steal syndrome due to the collateral pathway from the coronary artery may be considered a likely cause of the angina pectoris. The collateral circulation was considered to be an important route of blood flow supply to the brain and, at the same time, a cause of coronary steal syndrome and consequently angina pectoris.

Adult↗
PubMed1998

Proximal extracranial vertebral artery disease in the New England Medical Center Posterior Circulation Registry.

OBJECTIVE: To describe the clinical features of patients with occlusive disease of the proximal (V1) segment of the vertebral artery. DESIGN AND PATIENTS: Patients with either occlusion or high-grade stenosis involving the V1 segment were chosen for study from the New England Medical Center Posterior Circulation Registry. The registry is a consecutive series of patients with signs and symptoms of posterior circulation ischemia seen at the New England Medical Center, Boston, Mass, during a 10-year period. Clinical features, radiographic findings, and patient outcome were reviewed. RESULTS: Of the 407 patients in the registry, 80 (20%) had V1 segment lesions. Patients could be classified into 5 groups: (1) V1 disease and coexistent severe intracranial occlusive disease of the posterior circulation (n=22); (2) V1 disease with evidence of artery-to-artery embolism (n=19); (3) suspected V1 disease with artery-to-artery embolism, but with other potential causes of stroke or less certain vascular diagnosis (n=20); (4) V1 disease associated with hemodynamic transient ischemic attacks (n=13); and (5) proximal vertebral arterial dissection (n=6). Hypertension, cigarette smoking, and coronary artery disease were common risk factors. Clinical features, location of infarct, and outcome differed between groups and reflected the presumed mechanisms of stroke. CONCLUSIONS: Occlusive disease involving the V1 segment of the vertebral artery is common in patients with posterior circulation ischemia, but is often associated with other potential mechanisms of stroke. However, in a series of patients seen at a tertiary referral center, occlusive disease of the V1 segment was the primary mechanism of ischemia in 9% of patients.

Academic Medical Centers↗
PubMed1992

Urinary excretion of catecholamines and their metabolites in relation to circulating catecholamines. Six-hour infusion of epinephrine and norepinephrine in healthy volunteers.

Some depressed patients have been shown to excrete abnormal amounts of catecholamines and their metabolites in urine. Some studies suggest that hypersecretion of epinephrine by the adrenals and of norepinephrine by the peripheral sympathetic system cause increased excretion of urinary catecholamines and their metabolites in a subgroup of patients. To evaluate the effect of increased catecholamine levels in the peripheral circulation on urinary catecholamine and metabolite levels, we infused healthy volunteers during 6 hours with epinephrine, norepinephrine, or placebo, respectively, in a three-period, double-blind, crossover design. The results indicate that (1) urinary epinephrine and norepinephrine levels were the most sensitive indicators of increased circulating epinephrine and norepinephrine levels, respectively; (2) changes in circulating epinephrine or norepinephrine levels were not readily reflected in changes in urinary vanillylmandelic acid or 3-methoxy-4-hydroxyphenylglycol levels; and (3) increased normetanephrine excretion was not only induced by infusion of norepinephrine but also by epinephrine. This last finding may be due to activation of the sympathetic nervous system by circulating epinephrine. These results may help to explain the mechanism of adrenal epinephrine and sympathetic nervous system norepinephrine hypersecretion observed in subgroups of depressed patients.

Adult↗
PubMed1994

Ferric iron potentiates cell depolarization by a circulating shock protein.

OBJECTIVE: To determine whether or nor iron affects the depolarizing activity of a circulating shock protein that appears in plasma after hemorrhage. DESIGN: Randomized design. SETTING: University laboratory. ANIMALS: Healthy male Sprague-Dawley rats weighing 300 to 400 g with femoral artery and vein cannulas placed 4 days before hemorrhage. INTERVENTION: A 20-mL/kg hemorrhage and plasma collection. MAIN OUTCOME MEASURES: Depolarizing activity was measured as the increased fluorescence of an oxonol dye in the presence of Fe3+, Fe2+, or the iron chelator deferoxamine mesylate and was titrated against increasing concentrations of circulating shock protein or iron. Circulating shock protein was derived from plasma and was purified in two steps: stepwise ammonium sulfate precipitation followed by denaturing ion-exchange chromatography and refolding. RESULTS: At physiologic concentrations, Fe3+ but not Fe2+ potentiated the depolarizing activity of plasma after ammonium sulfate. Addition of deferoxamine abolished activity. Denaturing chromatography removed nearly all the depolarizing activity; however, Fe3+ restored activity to this fraction. Fe3+ increased total activity and decreased the concentration at which 50% activity was observed. CONCLUSION: These data indicate that physiologic concentrations of Fe3+ may act to modulate the depolarizing activity of circulating shock protein that in turn mediates the intracellular accumulation of salt and water in shock.

Animals↗
PubMed1998

Decreased numbers of circulating B cells in myeloma patients with reduction after conventional chemotherapy.

Reports of high numbers of circulating monotypic B cells in patients with multiple myeloma (MM) have recently been published. These cells, which were identified by their expression of CD19, were reported to be resistant to conventional chemotherapy and to represent the source of relapse. We examined blood samples from 48 patients before and 53 patients after glucocorticoid containing chemotherapy by dual color flow cytometry. The absolute count of CD19+B cells in patients before treatment (212.6+/-24.8 x 10(6)/l) was decreased compared to normal controls (P = .038). In the post-treatment group, circulating B cells were highly significantly lower than in untreated patients (45.23+/-6.69 x 10(6)/l. P < .001). This reduction was also seen in 26 patients, that were followed during chemotherapy. The cytoplasmic kappa/lambda ratio was within normal range before and after treatment with no difference according to the light chain isotype of the paraprotein. We conclude that circulating B cells are not increased in patients with MM, that the majority of these cells are polyclonal, and that conventional chemotherapy effectively reduces circulating B cells without leading to dominance of resistant monotypic cells.

ADP-ribosyl Cyclase↗
PubMed2000

Uptake of circulating insulin-like growth factor-I into the cerebrospinal fluid of normal and diabetic rats and normalization of IGF-II mRNA content in diabetic rat brain.

Brain injury has been prevented recently by systemic administration of human insulin-like growth factor-I (hIGF-I). It is widely believed that protein neurotrophic factors do not enter the brain from blood, and the mechanism by which circulating hIGF-I may be neuroprotective is uncertain. This investigation tested the hypothesis that hIGF-I is taken up into cerebrospinal fluid (CSF) from the circulation. (125)I-hIGF-I was injected subcutaneously into rats. The (125)I-IGF-I recovered from CSF and plasma were indistinguishable in size from authentic (125)I-hIGF-I on SDS-PAGE. An ELISA was used that detected immunoreactive hIGF-I, but not rat IGF-I, rat IGF-II, human IGF-II, or insulin. Osmotic minipumps were implanted for constant subcutaneous infusion of various hIGF-I doses. Uptake into CSF reached a plateau at plasma concentrations above approximately 150 ng/ml hIGF-I; the plateau was consistent with carrier-mediated uptake. The plasma, but not CSF, hIGF-I level was significantly reduced in streptozotocin diabetic vs. nondiabetic rats, and uptake of hIGF-I into CSF was nonlinear with respect to plasma hIGF-I concentrations. Nonlinear uptake excluded leakage or transmembrane diffusion of IGF-I from blood into CSF as a dominant route for entry, but the site and mechanism of uptake remain to be established. The IGF-II mRNA content per milligram brain (P < 0.02) as well as per poly(A)(+) RNA (P < 0.05) was significantly increased towards normal in diabetic rats treated by subcutaneous administration of hIGF-I vs. vehicle. This effect of circulating hIGF-I may have been due to regulation of IGF-II gene expression in the choroid plexus and leptomeninges, structures at least in part outside of the blood-central nervous system barrier. These data support the hypothesis that circulating IGF-I supports the brain indirectly through regulation of IGF-II gene expression as well as by uptake into the CSF.

Animals↗
PubMed2000

Vocal control region sizes of an adult female songbird change seasonally in the absence of detectable circulating testosterone concentrations.

Previous research established that in several species of seasonally breeding oscine birds, brain areas [vocal control regions (VCRs)] that control vocal behavior learning and expression exhibit seasonal plasticity, being larger during than outside the reproductive period. In adult males, this seasonal decrease correlates with circulating testosterone (T) concentrations. VCRs contain androgen receptors and T plays an important role in neural plasticity and in the control of singing behavior. In behaviorally dimorphic species, VCRs are larger in males than females and change seasonally also in females, but the dependency of these changes on circulating T levels in females has not been established. In free-living adult dark-eyed juncos (Junco hyemalis), a species in which females do not normally sing, the sizes of three VCRs (high vocal center, robust nucleus of the archistriatum, and Area X) were larger in males than females and decreased between summer and fall in both sexes. In males, this decrease was associated with changes in circulating T concentrations. Females, however, had on average undetectable T levels throughout the breeding season. Seasonal changes in VCR volumes in adult females may depend on very low (below detection limit) circulating T concentrations, on nonandrogenic plasma steroids, on androgen (or androgen metabolites) produced in brain tissues, and/or on nonsteroidal factors such as photoperiod or social interactions with conspecific birds.

Analysis of Variance↗
PubMed2000

Circulating serpin tumor markers SCCA1 and SCCA2 are not actively secreted but reside in the cytosol of squamous carcinoma cells.

An elevation in the circulating level of the squamous-cell carcinoma antigen (SCCA) can be a poor prognostic indicator in certain types of squamous-cell cancers. Total SCCA in the circulation comprises 2 nearly identical, approximately 45 kDa proteins, SCCA1 and SCCA2. Both proteins are members of the high-molecular weight serine proteinase inhibitor (serpin) family with SCCA1 paradoxically inhibiting lysosomal cysteine proteinases and SCCA2 inhibiting chymotrypsin-like serine proteinases. Although SCCA1 and SCCA2 are detected in the cytoplasm of normal squamous epithelial cells, neither serpin is detected normally in the serum. Thus, their presence in the circulation at relatively high concentrations suggests that malignant epithelial cells are re-directing serpin activity to the fluid phase via an active secretory process. Because serpins typically inhibit their targets by binding at 1:1 stoichiometry, a change in the distribution pattern of SCCA1 and SCCA2 (i.e., intracellular to extracellular) could indicate the need of tumor cells to neutralize harmful extracellular proteinases. The purpose of our study was to determine experimentally the fate of SCCA1 and SCCA2 in squamous carcinoma cells. Using subcellular fractionation, SCCA-green fluorescent fusion protein expression and confocal microscopy, SCCA1 and SCCA2 were found exclusively in the cytosol and were not associated with nuclei, mitochondria, lysosomes, microtubules, actin or the Golgi. In contrast to previous reports, metabolic labeling and pulse-chase experiments showed that neither non-stimulated nor TNFalpha/PMA-stimulated squamous carcinoma cells appreciably secreted these ov-serpins into the medium. Collectively, these data suggest that the major site of SCCA1 and SCCA2 inhibitory activity remains within the cytosol and that their presence in the sera of patients with advanced squamous-cell carcinomas may be due to their passive release into the circulation.

Amino Acid Sequence↗
PubMed1976

Effect of sialidase on the viability of erythrocytes in circulation.

Sialic acid has been detected on the erythrocyte surface of a number of different species of animals. The objective of this investigation was to determine the physiological significance of these sialyl residues to the viability of erythrocytes in circulation. Methods have been described for the determination of total sialic acid on red blood cells and the conditions under which it may be released with sialidase. Chicken, dog, goat, and rabbit were chosen for these studies because of the differences in the amount (3 X 10(6) - 72 X 10(6) resides per erythrocyte), and type (N-acetyl-or N-glycolyl-neuraminic acids) of sialic acid found on the surface of their erythrocytes. Radioactive tagging with Na251CrO4 was used to monitor the effect of sialidase on the viability of erythrocytes upon autologous transfusion. By the two criteria used to assess the viability of erythrocytes-the percentage of erythrocytes surviving 24 hr after the autologous transfusion, and the half-life of those red blood cells in circulation that survive the first 24 h after the autologous transfusion, and the half-life of those red blood cells in circulation that survive the first 24 hr-it is apparent that the presence of sialic acid on the cell surface is crucial for the survival of nonnucleated mammalian erythrocytes. The loss of viability of dog erythrocytes can be elicited by the removal of approximately 10% of the total sialic acid. In marked contrast to the behavior of mammalian erythrocytes, sialidase-treated chicken erythrocytes appear to retain their viability in circulation.

Animals↗
PubMed1992

Circulating CD34+ cells: an adverse prognostic factor in the myelodysplastic syndromes.

As part of an epidemiological survey of myelodysplastic syndromes (MDS) in southern Tasmania, 62 MDS patients identified over a 2 year period were tested for the presence of CD34, the human progenitor cell antigen (HPCA), in their peripheral blood. The results were correlated with transformation to acute myeloid leukemia (AML) and patient survival, and CD34+ status was compared as a prognostic indicator with Bournemouth score, cytogenetics, and CFU-GM colony growth which were also assessed. Circulating CD34+ cells were found in 23 of the 62 MDS patients; 9 of the 23 patients with circulating CD34+ cells transformed to AML, as compared with none of the 39 CD34 negative patients (P less than 0.0001); and 11 of the 23 patients with circulating CD34+ cells were dead at the end of the 2 year period, as opposed to 6 of the 39 with no CD34+ cells (P less than 0.03). The Bournemouth score was also significantly associated with transformation to AML (P less than 0.0001) and poor survival (P less than 0.04). These were the only significant associations of the possible prognostic factors studied with either transformation or survival. In summary, the presence of circulating CD34+ cells was significantly associated with both progression to AML and poor survival and was found to be a better prognostic indicator than cytogenetics or CFU-GM colony growth.

Adult↗
PubMed1994

Cephalic circulation in the air-breathing snakehead fish, Channa punctata, C. gachua, and C. marulius (Ophiocephalidae, Ophiocephaliformes).

The macrocirculation in the head of three air-breathing species of Channa was examined with the aid of vascular corrosion replicas and a scanning electron microscopic study was conducted on the pseudobranch, choroid gland and lentiform body. Two facultative air-breathing murrels, C. punctata and C. gachua, and one obligate air-breather, C. marulius were examined. In all three, the air-breathing organs (ABO) and systemic circulations were in-parallel, and both were in-series with the branchial circulation. Efferent branchial arteries from the first and second gill arches formed the arterial supply to the ABO, whereas the third and fourth arch efferents perfused systemic tissues. Postbranchial blood from the second gill arch also entered the systemic circulation directly via a shunt from the efferent branchial artery to the lateral aorta and via hypobranchial arteries. Vascular specialization to prevent mixing of oxygenated ABO venous and deoxygenated systemic venous blood was evident in arterial, but not venous circuits. Pseudobranchs of C. gachua and C. punctata are tri-lobed, in C. marulius they have numerous lobules. Pseudobranch lamellae are wider and shorter along the axis of blood flow than gill lamellae and folded perpendicular to this axis. Pseudobranch lamellae appear to be modified to minimize their epithelial surface while retaining an extensive vascular endothelial-pillar cell surface area, counter-current amplification is also possible. The choroid gland is an extensive planar counter-current capillary rete. The lentiform body of the eye is a globular capillary rete but there is no evidence of a counter-current circulation. The choroid and lentiform rete may have distinct physiological functions.

Air↗
PubMed1982

Circulating DNA in polyarteritis nodosa and related syndromes.

Patients with systemic lupus erythematosus (SLE) were previously reported to have a high prevalence of circulating DNA in association with systemic vasculitis. The present study was designed to determine whether circulating DNA also characterizes forms of systemic arterial inflammation other than those associated with SLE. A specific counterimmunoelectrophoresis assay capable of detecting 20-50 ng/ml of double-stranded DNA (dsDNA) in plasma was used. Of a total of 16 patients studied, 15 (94%) had circulating DNA. Similarly, 89% of the 47 plasmas from vasculitis patients contained DNA. In each of the 3 control groups, which consisted of normal individuals, patients with nonvasculitic systemic inflammation, and patients receiving high dose corticosteroid and/or cytostatic agents, no more than 8% had plasma DNA. This difference was significant with P less than 0.001. Relevance of this observation to etiologic, pathogenetic, and clinical considerations in the systemic arteritides is discussed. It is suggested that clinical detection of circulating plasma DNA may be useful for the diagnosis and management of systemic polyarteritis nodosa and related syndromes.

Adult↗
PubMed1985

Relationship between circulating interferon and anti-interferon antibodies and impaired natural killer cell activity in systemic lupus erythematosus.

Interferon (IFN) production and response are impaired in a high percentage of systemic lupus erythematosus (SLE) patients. In addition, elevated serum levels of alpha-IFN or anti-alpha-IFN antibodies are present in some SLE patients. This study examined the relationship of circulating IFN and anti-IFN antibodies to the impairment of natural killer (NK) cell function in SLE. All 15 SLE patients studied had measurable circulating alpha-IFN, while the normal controls had minimal serum IFN. Neither patient nor control sera contained any detectable anti-alpha-IFN activity. However, most of the SLE patients demonstrated defects in NK cell function. Because these defects in NK cell function appeared to be associated with circulating IFN, but not anti-IFN, antibodies, the effect of prolonged in vitro IFN exposure on NK cell function of peripheral blood mononuclear cells was determined. It was found that prolonged exposure to IFN induced both an apparent defect in IFN response and a definite impairment of baseline NK cell function. These results suggest that prolonged elevation of circulating alpha-IFN levels could be responsible, in part, for the defects in natural cytotoxicity present in SLE.

Autoantibodies↗
PubMed1993

Circulating soluble tumor necrosis factor receptors, interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-6 levels in rheumatoid arthritis. Longitudinal evaluation during methotrexate and azathioprine therapy.

OBJECTIVE: To assess whether circulating concentrations of soluble tumor necrosis factor receptors (sTNFR; p55 and p75), soluble interleukin-2 receptors (sIL-2R), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) reflect clinical response and whether changes are dependent on the drug used in rheumatoid arthritis (RA) patients taking methotrexate (MTX) or azathioprine (AZA). METHODS: These cytokines and soluble receptors were assessed in 20 control subjects and serially for up to 48 weeks in 61 RA patients, by bioassay (IL-6) and immunoassays (sTNFR, sIL-2R, TNF alpha, and IL-6). RESULTS: Concentrations of p55 and p75, sIL-2R, and TNF alpha (but not IL-6) were significantly higher in RA patients than in controls. Significant decreases in sIL-2R and p55 concentrations were associated with clinical improvement and were observed in patients treated with MTX, but not AZA. Both treatments induced decreases in IL-6 concentrations, but circulating AZA (or its metabolites) appears to interfere with the measurement of IL-6 bioactivity. TNF alpha and p75 levels did not show significant changes. CONCLUSION: Measurement of circulating sIL-2R, p55, and IL-6 may be useful in the evaluation of RA disease activity and response to therapy. Interference by circulating levels of drugs must be ruled out when bioassays are used to evaluate cytokine levels.

Arthritis, Rheumatoid↗